The production of specialty chemicals, such as polymeric and pharmaceutical materials, is an important aspect of the global economy. Many such chemicals are responsible for an improved life style. However, the production of specialty chemicals is time consuming and often inefficient.
Dendrimers are an example of a specialty chemical that can be produced by typical synthetic methodology. Dendrimers are nanoscale macromolecules that have highly branched and core-shell structures with hollow internal voids and a number of peripheral functionalities. They are synthesized stepwise manner to form higher generations using a plethora of chemical reactions. The chemistry of the core and the terminal functionalities can be tailored according to the specific application.
Dendrimers have tremendous potential, but the conventional synthetic approach is time-consuming. Since the first dendrimer synthesis in the late 1980's [D. A. Tomalia, H. Baker, J. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder and P. Smith, Polym. J. (Tokyo), 17, 117 (1985)] dendrimers have found many applications, including catalysis [C. Bohm, N. Derrien, A. Seger, Synlett, 387(1996)]; sensors, [M. Wells, R. M. Crooks, J. Am. Chem. Soc., 16, 3988(1996)]; and drug delivery and light harvesting [M. Freemantle, C&EN, 77, 27 (1999)]. Higher generation dendrimers have close packed, peripheral functional groups and a hollow interior. This unique feature provides a high capacity to act as hosts to encapsulate guests in the interior and conjugate molecules on the surface. Their nanometer size allows them to easily penetrate into cells. Along with targeting tumor and other cells as drug delivery systems, dendrimers have shown promising results as tools for MRI imaging and gene transfer techniques. Also, dendrimer-based nanocomposites are being studied as possible antimicrobial agents to fight Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. L. Balogh, A. Bielinska, J. D. Eichman, R. Valluzi, and others. Dendrimer Nanocomposites in Medicine. The University of Michigan Center for Biologic Nanotechnology, Tuff Biotechnology Center and Department of Radiation Oncology at The University of Michigan. Dendrimers have been shown to act as scavengers of metal ions, offering the potential for use in environmental clean-up applications. Their size allows them to be filtered out post-extraction using common ultrafiltration techniques. Recently, Le Berre et al. [Le Berre, Nucleic Acids Res. 2003, 31 (16) 88] described attaching dendrimeric coating to glass slides for sensitive DNA microarray analysis. Again acting as scavengers, dendrimers have been employed for rapid purification in solution-phase, parallel synthesis. L. Williams and S. M. Neset, Fourth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-4), Sep. 1-30, 2000, Paper No. B0011.
Dendrimers can be synthesized with great precision. Ideally a certain generation of dendrimer has a single size and molecular weight rather than a broad molecular weight distribution like linear polymers. Kim, R. M.; Manna, M.; Hutchins, S. M.; Griffin, P. R.; Yates, N. A.; Bernick, A. M.; Chapman, K. T. Proc. Natl. Acad. Sci. USA 1996, 93, 10012-10017. But, in many cases, the limiting factor on the application of dendrimers is their production cost. Two general approaches to dendrimer synthesis exist. The divergent approach, arising from the seminal work of Tomalia and Newkome, initiates growth at the core of the dendrimer and continues outward by the repetition of coupling and activation steps. Convergent synthesis, first reported by Hawker and Fréchet in 1989 [J. M. J. Fréchet, Y. Jiang, C. J. Hawker, A. E. Philippides, Proc. IUPAC Int. Symp., Macromol. (Seoul), 19-20, 1989], initiates growth from the exterior of the molecule, and progresses inward by coupling end groups to each branch of the monomer. More recently, creative synthetic strategies that combined both divergent and convergent synthesis have also been developed by dendrimer chemists. A. Archut, S. Gestermann, R. Hesse, C. Kaufmann, F. Vögtle, Synlett, 546-548, 1998. The first reported dendrimer, polyamidoamine (PAMAM), is probably the most studied dendrimer. In 1985 and 1986, Tomalia et al. [.A. Tomalia, H. Baker, J. Dewald M. Hall, G. Kallos, S. Martin, J. Roeck, J. Ryder, and P. Smith, Macromolecules, 19(9), 2466-2468, (1986)] described the preparation of PAMAMs by the divergent approach. The synthesis involved in situ branch cell construction in step-wise, iterative stages around a desired core (e.g. ammonia or ethylenediamine (EDA)) to produce defined core-shell structures. For EDA-cored PAMAM as an example, the typical synthesis takes 24 hours for half generations and 96 hours for full generations. M. J. Frechet, D. A. Tomalia, Dendrimers and other dendritic polymers. John Wiley & Sons Ltd. (2001).
In half generations of PAMAM the terminal functionality is an ester; for full generations the terminal functionality is an amine. The structure of a generation-2 EDA—cored PAMAM is shown below.

In view of the importance of specialty chemicals, such as dendrimers, new methodologies for their synthesis are desirable. The present invention provides such a new methodology, as well as “nanofactories” designed to synthesize such chemicals cleanly, quickly and efficiently.